1,3-Oxazoline and 1,3-oxazine compounds have found use in a variety of procedures. Both classes of compounds have been used as monomers in ring opening polymerizations and have been used as protecting groups for carboxyl moieties in organic synthesis. Additionally, chiral oxazolines have proven useful for selected asymmetric syntheses. Also, oxazine and oxazoline derivatives have a variety of biological activities.
Prior syntheses of 1,3-oxazolines and 1,3-oxazines have followed several routes. For example, the reaction between amino alcohols and nitriles is a convenient synthesis, but fails in some instances. Dehydration of .gamma.-hydroxy amides also a common technique, but requires both harsh conditions and a special experimental setup and procedures. Another important method is ring closure of .gamma.-halo amides under basic conditions. This procedure usually involves aqueous or alcoholic conditions with the base in high concentration.
Ando et al. have shown that 40% potassium fluoride on neutral alumina is a convenient and efficient reagent for the N-alkylation of amides. However, it does not appear that such a solid supported fluoride reagent has been previously used in an intramolecular ring closure reaction.
In exploring the syntheses of 1,3-oxazolines and 1,3-oxazines, the applicants have now discovered that potassium fluoride on an inorganic solid substrate such as neutral alumina is an effective reagent in converting N-(.beta.-haloalkyl)amides to 1,3-oxazolines and N-(.gamma.-haloalkyl)amides to 1,3-oxazines in an intramolecular ring closing reaction. This discovery has lead to a variety of developments in this area.
Accordingly, it is an object of the present invention to provide a method of synthesizing oxazolines and oxazines using an alkali fluoride, such as potassium fluoride, supported on an inorganic solid substrate such as alumina as a reagent.
It is another object of this invention to provide a method of synthesizing oxazolines and oxazines under relatively mild conditions, i.e., at room temperature using potassium fluoride on an inorganic solid substrate such as alumina as a reagent.
It is still another object of the present invention to provide a method of synthesizing oxazolines and oxazines in high yield using potassium fluoride on alumina as a reagent.